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Diversity, development and immunoregulation of enteric neurons.

Marklund, U.

Nature Review Gastroenterology & Hepatology. 2022 Feb;19(2):85-86. PMID: 34773107

In this review I summarise key advances in enteric neuroscience in 2021. Morarach et al presented a molecular definition of enteric neuron classes (ENCs) and and a new model for their embryonic specification. Elmentaite et al published a comprehensive gut cell atlas including the developing ENS and its surrounding cell types. Yan et al discovered a role for the ENS in tuning regulatory T-cells. 

Diversification of molecularly defined myenteric neuron classes revealed by single cell RNA-sequencing.

Morarach K, Mikhailova A, Knoflach V, Memic F, Kumar R, Li W, Ernfors P, Marklund U.

Nature Neuroscience. 2021 vol 24 (1) 34-46. PMID: 33288908

By single-cell transcriptomics our study revealed 12 Enteric Neuron Classes (ENCs) in the myenteric plexus of mice, which were validated in vivo. Interestingly, the study suggested that enteric sensory neurons may be heterogeneous and thus subserve different functions. Further scRNA-seq analysis of the developing gut identified that the enteric neuron classes emerge from a neurogenic binary cell fate decision followed by postmitotic identity transitions.

Molecular architecture of the mouse nervous system.

Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F, van der Zwan J, Häring M, Braun E, Borm L, La Manno G, Codeluppi S, Furlan A, Skene N, Harris KD, Hjerling- Leffler J, Arenas E, Ernfors P, Marklund U, & Linnarsson S.

Cell. 2018 174(4):999-1014. PMID: 30096314

We participated in the collaborative effort to define every neuron of the mouse body, we almost succeeded! The atlas includes our first sc-RNA sequencing dataset of the myenteric neurons, but also the enteric glia (10 000 cells). Easily accessible to explore at:

Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System.

Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J, Sundström E, Pachnis V, Marklund U.

Gastroenterology. 2018 154:624-636. PMID:  29031500

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We used transcriptome profiling of lineage traced cell populations to assess the temporal development of the ENS. We identified 100s of new transcription and signaling factors. Validation of the new factors in vivo revealed a striking resemblance between the murine and human developing ENS. One of the identified transcription factors (Sox6) was demonstrated to be essential for gastric dopaminergic cell formation and gastric motility.

Ascl1 is required for the development of specific neuronal subtypes in the enteric nervous system.

Memic F, Knoflach V, Sadler R, Tegerstedt G, Sundström E, Guillemot F, Pachnis V and Marklund U.

Journal of Neuroscience. 2016 April 36(15): 4339-50. PMID: 27076429

Using transgenic knockout/knockin mice we revealed that the proneural gene Ascl1 not only is required for a normal timing of neurogenesis in the ENS, but also for the correct generation of enteric neuronal subtypes.

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